This laboratory proposes to continue its morphological and molecular biological studies of retinoblastoma and uveal melanoma and interface them with new technologies made available through recombinant DNA research. Specifically we plan the following studies: 1. We will study a transgenic mouse that develops heritable retinoblastoma due to the genomic integration of a gene coding for SV40 large T antigen. The morphology, molecular biologic features, site of large T antigen integration, and elucidation of transgenic regulatory elements will be determined. These studies should reveal similarities an differences between murine tumor and human retinoblastoma and will establish the transgenic mouse model's concordance with the human condition. 2. In situ hybridization will be utilized to study expression of retinoblastoma gene in developing mature retina and other tissues. Variations of expression for different cell types will be investigated in order to define the histogenesis of retinoblastoma and the role of the Rb gene in differentiating tissue. 3. We will assay for oncogene activations in naturally occurring human uveal melanoma and correlate presence of oncogene activation with cell type and prognosis. In addition we have described the inhibition of retinoblastoma growth by vitamin D compounds and sodium butyrate and we will continue to study potential therapeutic strategies in the transgenic mouse model of retinoblastoma.